Mathematical modeling can provide insight into a mechanism or process, and can be used to make predications that can be tested experimentally. The long-term goal of the proposed work is to develop a multiscale model that will increase understanding of the human focusing mechanism (accommodation) and the age-related loss of accommodative range (presbyopia). Presbyopia is a multifactorial process, the mechanism of which remains the subject of controversy and disagreement, as does the accommodation mechanism itself. Understanding how presbyopia develops may ultimately lead to strategies for slowing or stopping the process. It is even more important in developing new designs for intraocular lens implants that can take advantage of the eye's unique focusing system to restore a measure of accommodative amplitude. It is the hypothesis of this senior fellowship proposal that most or all of the information necessary to understand the human accommodation mechanism is currently available in the literature, but not in an organized form. This long-term goal has been broken down into three specific aims. Aim 1 is to create an updated and expanded analytic biomechanical model of the crystalline lens and ciliary muscle in human accommodation, using well-defined strain tensor elements as the basis for inverse calculations leading to the incremental change in tractions and forces with an incremental change in refraction. This model will be complemented by a finite element representation using the same data sets and assumptions. Aim 2 is to create an updated and expanded model of image formation by the eye, using paraxial and non-paraxial ray- tracing approaches to test current and theoretical ideas about the shape of the refractive index gradient. This will be used to correlate optical function with biomechanical changes in lens shape, both on the surface and internally. Aim 3 will be concerned with the biomechanical and optical constraints created by crystalline lens structural organization and ultrastructure, and will be the bridge linking the molecular and macromolecular properties of the lens fiber cells with lens function in accommodation. Presbyopia is the most common visual disorder of people aged 40 and over, and, according to the National Eye Institute, "represents a significant economic cost to society". The way that the focusing process changes with aging can provide clues for ways to arrest or slow the loss of visual range. It is also important in the design of intraocular lens implants that can effectively restore focusing ability. [unreadable] [unreadable] [unreadable]